This project is designed to evaluate regional myocardial perfusion in the intact dog at rest and during treadmill exercise with unimpeded coronary inflow, in the presence of a proximal coronary stenosis, and following total occlusion of a major coronary artery. These studies will examine the determinants of the transmural distribution of myocardial blood flow during normal conditions and in the presence of myocardial ischemia. In addition, the character of the perfusion boundary which surrounds a region of ischemic myocardium following coronary artery occlusion will be studied. Interventions which may alter transmural myocardial perfusion to alleviate the severity of subendocardial ischemia in areas of restricted coronary inflow will be tested. The long-term goal of this research is to characterize those factors which mediate the vulnerability of the subendocardium to ischemia and infarction, and to evaluate interventions which may alter that vulnerability.